Download Tumour markers in the clinical ... small cell lung cancer M Hansen,

Eur Respir J
1989, 2. 700-701
EDITORIAL
Tumour markers in the clinical management of patients with
small cell lung cancer
M. Hansen, H.H. Hansen*
Neoplastic cells produce and release several substances.
Some of these substances are produced specifically by
certain tumour types, making it possible to use these
substances as tumour markers. The latter implies that
they can be used in the histopathological classification
and, provided the substances can be measured in blood
or urine, also in the clinical management of patients, e.g.
in screening, diagnosis, staging, prognostication, therapy
monitoring, including evaluation of tumour response and
early relapse. Well-known examples of clinically useful
tumour markers are amines in carcinoids and pheocromocytomas, and the M-component in myeloma. In recent
years, human chorionic gonadotrophin (HCG) and alpha
foetoprotein have contributed significantly to the
diagnosis and treatment of germ cell tumours, including
testicular cancer.
For patients with lung cancer in general, carcinoembryonic antigen (CEA) was one of the first markers
described. The concentration of this marker has been
found to be related to the prognosis and tumour burden
in groups of patients with small cell lung cancer (SCLC),
but CEA has no significant predictive value for the
individual patient.
Among the various histological cell types, SCLC has
been known to produce a series of tumour makers compatible with the neuro-endocrine histological
origin of SCLC from the amine precursor uptake and
decarboxylation (APUD)-system. Already in 1928 a
patient with small cell lung cancer was described with
the ectopic Cushing syndrome a few years before Cushing described the syndrome related to his name in nonmalignant cases [1].
Subsequently, it was recognized that endocrine
syndromes, such as the ectopic Cushing syndrome and
the Schwartz-Barrter syndrome (SIADH) in lung cancer
were particularly related to SCLC [2, 3].
During the 1970's considerable progress was made in
the cytostatic treatment of SCLC with a subsequent
interest in identification of tumour markers in order to
improve the clinical management of patients with SCLC.
Initially, the hormonal peptides were investigated, and
ACTH, ADH and calcitonin were classified as being
special hormonal markers for SCLC. However, measurement of these markers was not found to contribute
significantly to the clinical management of patients with
SCLC [3).
•Dept of Internal Medicine F, Hillerlld, Denmark and Dcpt of
Oncology, The Finsen InstituteJRigshospitalet, Copenhagen, Denmark.
Within the present decade, gastrin-releasing peptide
(GRP), has often been found to be produced by SCLC
cell lines [4]. This was initially identified as bombesin,
which is an amphibian peptide of 14 amino acids. The
bombesin-like immunoreactivity is due to the first 14 of
the 27 amino acids in GRP. Cells with GRP are rare in
the normal adult lung, but are regularly found in the fetal
and infantile epithelium of the lung (5). It is particularly
noteworthy that SCLC is often equipped with receptors
for GRP [6], which has a growth promoting activity in
SCLC [7). Accordingly, it has been suggested that GRP
acts as an autocrine growth factor in SCLC.
Unfortunately, increased concentrations of GRP in the
serum are rare [4, 8] due to its very short half-life.
Recently, a radioimmunoassay for pro-GRP has been
developed. Using this assay, elevated plasma concentrations were found in 72% of 71 SCLC patients [9]. Further
clinical studies are at present in progress to define a
possible role of pro-GRP as a clinically useful tumour
marker in SC.LC.
ln addition to different hormonal peptides, some
enzymes were also detected in the cell lines derived from
SCLC tumours, i.e. the brain fractions of enolase and
creatine kinase (CK), known as neuron-specific enolase
(NSE) and CK BB. The latter enzyme has been noted to
be elevated in about half of the patients with SCLC,
particularly in patients with extensive disease, but a
clinical role of this marker has not yet been defined.
In contrast, NSE has been extensively tested in SCLC
[10]. It has been found to be elevated in about 70% of
SCLC patients with values of 50% in patients with
localized disease and 85% in extensive stage patients.
Recently, it was also demonstrated that NSE may be an
important prognostic factor [11, 12). The relation to stage
is also found in the individual patients, as it has preliminarily been observed that the concentration of NSE decreases with response and increases some weeks before
the clinical recognition of relapse [13]. In patients with
non-SCLC, NSE is found to be elevated in only 10-15%,
and in this group of patients, the concentrations are almost
always below 25 ng·ml·1 • Accordingly, NSE may be diagnostic for SCLC if the concentration is above this level,
whereas at lower concentrations it is of no diagnostic
value [14].
On the other hand, a recent publication observed that
the demonstration of NSE in non-SCLC tumour tissue
predicts a much better response to chemotherapy than
has usually been noted in non-SCLC patients [15). This
TUMOUR MARKERS IN SMALL CELL LUNG CANCER
phenomenon should be further investigated, including a
possible predictive value for response of an elevated serum
NSE-concentration in non-SCLC.
In the future, NSE may be included as a tumour marker
in the management of SCLC patients, but at least one
more large prospective study is necessary for a more
exact defmition of its role in the routine clinic.
References
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Cancer, 1968, 22, 274-286.
3. Hansen M. - Clinical implications of ectopic hormone
production in small cell carcinoma of the lung. Dan Med Bull,
1981, 28, 221-236.
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production by human small cell carcinoma of the lung. Regul
Pept, 1982, 4, 59-66.
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701
7. Camey DN, Cuttita F, Moody TW, et al.- Selective stimulation of small cell lung cancer clonal growth by bombesin and
gastrin-releasing peptide. Cancer Research, 1987,47, 821-825.
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concentrations of GRP C-flaning peptide in small cell lung
cancer, (in preparation).
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small cell lung cancer. Cancer, 1988, 62, 125-134.
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cancer. Eur J Cancer Clin Oncol, 1989, 25, 123-128.
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cancer. Eur J Cancer Clin Oncol, 1987, 23, 171-176.
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